From a Sequential to a Concurrent Reaction in Aqueous Medium: Ruthenium‐Catalyzed Allylic Alcohol Isomerization and Asymmetric Bioreduction

Abstract

The ruthenium-catalyzed redox isomerization of allylic alcohols was successfully coupled with the enantioselective enzymatic ketone reduction (mediated by KREDs) in a concurrent process in aqueous medium. The overall transformation, formally the asymmetric reduction of allylic alcohols, took place with excellent conversions and enantioselectivities, under mild reaction conditions, employing commercially and readily available catalytic systems, and without external coenzymes or cofactors. Optimization resulted in a multistep approach and a genuine cascade reaction where the metal catalyst and biocatalyst coexist from the beginning.

Overcoming the Incompatibility Challenge in Chemoenzymatic and Multi‐Catalytic Cascade Reactions

“…After the identification of alcohol dehydrogenases with the capacity to operate at 50 °C, the allylic isomerization was successfully coupled to the stereoselective enzymatic ketoreduction. The conversion of a series of allylic alcohols resulted in high isolated yields and excellent enantiopurity of the products . Again, this interesting example underlines that concurrent one‐pot cascade reactions are possible, but not always necessary and not generally applicable.…”

Asymmetric Reduction of Prochiral Ketones by Using Self‐Sufficient Heterogeneous Biocatalysts Based on NADPH‐Dependent Ketoreductases

“…For the synthesis of secondary alcohols (R)-2b and (S)-2 c,t he co-immobilized NADPH and KRED accumulatedaT TN of 333 and nearly 20000, respectively.T hese are the highest accumulated TTN presented in this study;t he values were lower for the other products because either the catalystl oading was higher( ( R)-2e-k) or the substrate concentration was lower ((R)-2a and d)o wing to solubility issues. [30] By using as imilara pproach, Merck &C o. co-immobilized NADPH and ad ifferent KRED from the same commercial source on commercial EC-HFAp orous beads to obtain good reusability by using av ery high IPAc oncentration (90 %). The highest TOF values were found for the synthesis of secondary alcohols (R)-2b and( S)-2c,w hich indicates that KRED has ap reference for these two substrates.…”

“…More recently, NADH and enzymes have been co-immobilized onto solidphase carriers,w hich gives rise to self-sufficienth eterogeneous biocatalysts that do not require exogenous cofactor supply during the reaction. [5,30] By using porousa garose beads that were activated with tertiarya mine groups, we fabricated one self-sufficient heterogeneous biocatalyst, in which both KRED and NADPH residues were co-immobilized and co-localized on the same surface; this enabled the enzymatic utilization of the cofactor and avoided its lixiviation. [25][26][27][28] In an industrial context, the most promising approach is the electrostatic adsorption of cofactors ande nzymest os olid and porousm aterials.…”

One-Pot Combination of Metal- and Bio-Catalysis in Water for the Synthesis of Chiral Molecules

“…Again, we firstly tested the catalytic activity of the aforementioned bis(allyl)-ruthenium(IV) Complexes 1-3 ( Figure 1) in the isomerization of a set of allylic alcohols in the medium required by KREDs (phosphate buffer containing i PrOH as the hydrogen source) [28]. In this case, only the acetate-Ru(IV) Complex 2 retained its high catalytic activity (99% conversions in 1-10 h) and selectivity, as undesired simultaneous reduction of the obtained ketones (through Ru-catalyzed transfer hydrogenation [41]) was not observed.…”